WO2019219823A1 - Dispersion solide contenant du ritonavir - Google Patents

Dispersion solide contenant du ritonavir Download PDF

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Publication number
WO2019219823A1
WO2019219823A1 PCT/EP2019/062639 EP2019062639W WO2019219823A1 WO 2019219823 A1 WO2019219823 A1 WO 2019219823A1 EP 2019062639 W EP2019062639 W EP 2019062639W WO 2019219823 A1 WO2019219823 A1 WO 2019219823A1
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WO
WIPO (PCT)
Prior art keywords
solid dispersion
ritonavir
pharmaceutical composition
cationic polymer
disintegrant
Prior art date
Application number
PCT/EP2019/062639
Other languages
English (en)
Inventor
Panagiotis PANAGOPOULOS
Konstantinos-Emmanouil PANITSAS
Konstantinos KOMPOROZOS
Aggelos Likoudis
Matthaios Syrigos
Maria Hatzouli
Charalambos PATTIHIS
Antje NORDMANN
Michalis NEOPTOMEMOU
Original Assignee
Pharmaceutical Oriented Services Ltd.
Remedica Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmaceutical Oriented Services Ltd., Remedica Ltd filed Critical Pharmaceutical Oriented Services Ltd.
Priority to EP19725121.8A priority Critical patent/EP3793530A1/fr
Publication of WO2019219823A1 publication Critical patent/WO2019219823A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer

Definitions

  • the present invention relates to a solid dispersion containing ritonavir and to its use in the preparation of a solid pharmaceutical composition.
  • Ritonavir has a low solubility in aqueous media as well as low membrane permeability, so that this drug is classified as a class IV compound according to the Biopharmaceutics Classification System (BCS).
  • Class IV drugs are generally difficult to be formulated as a unit dosage form for oral administration, because adequate oral bioavailability cannot easily be achieved.
  • lipid based delivery systems e.g. lipid based delivery systems, polymer based nano-carriers, crystal engineering (nano-crystals and co-crystals), liquisolid technology and self-emulsifying solid dispersions
  • Self-emulsifying solid dispersions consist of a dispersion of the drug in an inert excipient matrix, where the drug may exist in finely divided crystalline or amorphous states or in a molecularly dispersed form (solid solution).
  • Typical self-emulsifying polymers which may be employed as pharmaceutical excipients constituting the matrix of the solid dispersion, are lauroyl polyoxylglycerides (e.g. PEG-32 lauroyl polyoxylglyceride (Gelucire ® 44/14)), tocopheryl polyethylene glycol 1000 succinate (TPGS) or polyoxyethylene/polyoxy- propylene copolymer (poloxamer (Pluronics ® )).
  • lauroyl polyoxylglycerides e.g. PEG-32 lauroyl polyoxylglyceride (Gelucire ® 44/14)
  • TPGS tocopheryl polyethylene glycol 1000 succinate
  • polyoxyethylene/polyoxy- propylene copolymer polyoxyethylene/polyoxy- propylene copolymer
  • Ritonavir is marketed under the tradename Norvir ® in the form of a soft capsule or tablet.
  • a fixed combination of ritonavir and lopinavir is marketed under the tradename Kaletra ® in the form of a soft capsule or tablet.
  • the mono and the combination product are indicated in combination with other antiretroviral agents for the treatment of HIV- 1 infection.
  • ritonavir Two polymorphs of ritonavir (forms I and II) are known. The preparation of these forms as well as the preparation of amorphous ritonavir is described in WO 00/04016.
  • Form II is the thermodynamically stable form and is much less soluble than form I.
  • the Norvir ® and Kaletra ® soft capsules were developed in order to suppress the formation of the form II.
  • the Norvir ® soft capsule contains a solution of ritonavir in ethanol, oleic acid, water and polyoxyl 35 castor oil. In the Kaletra ® soft capsule, propylene glycol is used instead of ethanol.
  • the crystallization of form II ritonavir is suppressed if the capsules are stored at 5 °C.
  • the Norvir ® and Kaletra ® film-coated tablets show, compared to the soft capsule formulations, both improved storage stability (the tablets may be stored at room temperature without formation of form II ritonavir) and enhanced oral bioavaila bility.
  • the tablet cores contain copovidone, sorbitan monolaurate, colloidal anhydrous silica and sodium stearyl fumarate, whereby the Norvir ® tablet additionally contains anhydrous calcium hydrogen phosphate.
  • the tablets are prepared by hot-melt extrusion, which affords a solid solution of the active substances in the matrix.
  • the main excipient is copovidone, a copolymer of vinylpyrrolidone and vinyl acetate (60 %/40 %).
  • WO 01/34118 describes a solid dispersion containing ritonavir.
  • the matrix is formed by a water-soluble carrier, e.g. by polyethylene glycol (PEG), poloxamer, polyoxy ethylene stearate or poly-e-caprolactone.
  • PEG polyethylene glycol
  • the solid dispersion is prepared by dissolving ritonavir in an organic solvent, preferably ethanol, dissolving the drug in the water-soluble polymer by adding the polymer to the solution and removing the organic solvent by evaporation.
  • the preferred water-soluble polymer is PEG.
  • the dissolution rate of ritonavir depends on the drug load: the higher the drug load, the lower the drug release from particles containing ritonavir dissolved in PEG.
  • the in vitro dissolution profile correlates with the oral bioavailability; the best oral bioavailability was found with the lowest drug load.
  • WO 2005/039551 and WO 2006/091529 relate to the Kaletra ® tablet. They describe a solid solution containing ritonavir and lopinavir within a water-soluble polymer, whereby the solid solution is prepared by hot-melt extrusion.
  • the preferred water- soluble polymer is copovidone.
  • the blend to be subjected to melt-extrusion should contain a surfactant having a hydrophilic-lipophilic balance (HLB) value of 4-10.
  • HLB hydrophilic-lipophilic balance
  • the preferred surfactants are sorbitan monolaurate and sorbitan monopalmitate.
  • WO 2009/081174 discloses a bilayer tablet containing darunavir in one layer and ritonavir in the other layer. It is stated in the application that the drugs may be dissolved/dispersed by hot-melt extrusion within a matrix containing a water-soluble and/or water-insoluble polymer, whereby the drug : polymer ratio should range from 1 : 1 to 1 : 6.
  • the preferred water-soluble polymer is copovidone, while examples of water-insoluble polymers include acrylic copolymers (e.g. Eudragit ® E), polyvinyl acetate, ethyl cellulose and cellulose acetate.
  • the darunavir-layer is preferably prepared by wet-granulation in which a mixture of darunavir, microcrystalline cellulose and crospovidone is treated with a polyvinylpyrrolidone-containing aqueous solution.
  • the ritonavir-layer is preferably prepared by holt-melt extrusion of a mixture containing the drug, copovidone and sorbitan monolaurate or polyoxyethylene castor oil (Cremophor ® ).
  • the ritonavir-containing tablets described in the prior art solve the oral bioavailability problem of the BCS class IV drug ritonavir by formulating the drug as a solid dispersion, i.e. by dissolving the drug in a self-emulsifying water-soluble polymer matrix.
  • a self-emulsifying polymers as Gelucire ® 44/14, TPGS or poloxamers
  • a combination of a water-soluble polymer and a surfactant is employed. It was an objective of the present invention to provide an alternative ritonavir-containing pharmaceutical composition, in which the formation of crystalline ritonavir, in particular of form II ritonavir is suppressed and which shows adequate oral bioavailability. This objective is attained by the subject matter as defined in the claims.
  • the present invention relates to a solid dispersion comprising ritonavir, a cationic polymer containing an amino group, and optionally a pharmaceutical excipient. It is preferred that the solid dispersion contains ritonavir in a molecularly dispersed form (solid solution). In another embodiment of the present invention, the solid dispersion may contain particles of ritonavir in the amorphous state.
  • the solid dispersion of the present invention serves the purpose of enhancing oral bioavailability of ritonavir.
  • the drug dissolves along with the cationic polymer containing an amino group to create a supersaturated solution.
  • the drug may crystallize, so that the dissolution advantage of the solid dispersion is lost.
  • the crystallization of ritonavir was suppressed by suspending the drug in a matrix of a water-soluble polymer and a surfactant. According to the present invention, no surfactant is required if ritonavir is dispersed in a cationic polymer containing an amino group.
  • a cationic polymer containing an amino group suppresses the crystallization of ritonavir in the gastrointestinal fluid.
  • Cationic polymers with amino groups have water solubility at acidic pH but not at neutral pH or above pH 7. This is achieved by the presence of the amino group that is protonated under acidic conditions.
  • the cationic polymer used in the present invention is soluble in water at a pH of 6.5 or below, preferably at a pH of 6 or below. It is assumed that the water penetration into the solid dispersion is delayed until the solid dispersion reaches the stomach. In the stomach (pH 1-3.5) the solid dispersion dissolves due to the protonation of the cationic polymer.
  • the weight ratio of the cationic polymer to ritonavir is usually 6 : 1 to 1 : 2, preferably 3 : 1 to 2 : 3, more preferred 3 : 2 to 1 : 1.
  • the cationic polymer is selected from aminoalkyl methacrylate copolymer, polyvinylacetal diethylaminoacetate and chitosan.
  • aminoalkyl methacrylate copolymer butyl methacrylate/(2-dimethylaminoethyl)- methacrylate/methyl methacrylate copolymer (1 : 2 : 1), which is marketed under the tradename Eudragit ® E, may be used.
  • Chitosan is soluble in water at a pH of 6.5 and below; Eudragit ® E is soluble in water at a pH of 5 or below, while polyvinylacetal diethylaminoacetate is soluble in water at a pH of 5.8 and below.
  • the solid dispersion of the present invention may contain a pharmaceutical excipient selected from a filler, a disintegrant and a surfactant.
  • fillers examples include microcrystalline cellulose, calcium hydrogen phosphate (anhydrous or dihydrate), lactose (anhydrous or monohydrate), calcium carbonate, magnesium carbonate, silicified microcrystalline cellulose, powder cellulose and mannitol.
  • the filler is selected from microcrystalline cellulose, powder cellulose, silicified microcrystalline cellulose and calcium hydrogen phosphate, whereby microcrystalline cellulose is most preferably used.
  • disintegrants examples include sodium starch glycolate, croscarmellose sodium and crospovidone, whereby the most preferred disintegrant is crospovidone.
  • surfactants include polyoxyethylene stearate, sodium lauryl sulphate, sorbitan fatty acid esters (e.g. sorbitan monolaurate or sorbitan monopalmitate), polyoxyethylene sorbitan fatty acid esters (e.g. Polysorbate 80) and polyoxyethylene castor oil.
  • sorbitan fatty acid esters e.g. sorbitan monolaurate or sorbitan monopalmitate
  • polyoxyethylene sorbitan fatty acid esters e.g. Polysorbate 80
  • polyoxyethylene castor oil e.g. Polysorbate 80
  • the solid dispersion consists of ritonavir, the cationic polymer, a filler and a disintegrant.
  • the cationic polymer is an aminoalkyl methacrylate copolymer, e.g. butyl methacrylate/(2-di- methylaminoethyl)methacrylate/methyl methacrylate copolymer (1 : 2 : 1)
  • the filler is microcrystalline cellulose
  • the disintegrant is crospovidone.
  • the present invention also relates to a pharmaceutical composition for oral administration containing the solid dispersion of the present invention.
  • the pharmaceutical composition may contain, besides the pharmaceutical excipients optionally contained in the solid dispersion, a filler, disintegrant and surfactant, which may be identical to those contained in the solid dispersion.
  • the pharmaceutical composition may, additionally, contain a binder, a glidant and/or a lubricant.
  • binders examples include hydroxypropyl methylcellulose (HPMC), methylcellu- lose, hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (povidone), polyvinyl alcohol, a vinylpyrrolidone/vinyl acetate copolymer (e.g. copovidone) and pregelati nized starch.
  • glidants examples include silicon dioxide (silica) and magnesium silicate.
  • lubricants examples include magnesium stearate, calcium stearate, zinc stearate, talc, sodium stearyl fumarate and glyceryl dibehenate.
  • the pharmaceutical composition of the present invention may be a tablet (including multiparticulate drug delivery systems) or a capsule that contains the solid dispersion of the present invention as particles (powder, granules or pellets), optionally in admixture with pharmaceutical excipients, and/or as minitablets.
  • the pharmaceutical composition of the present invention is preferably a tablet optionally coated with a film-coating.
  • a film-coating Commercially available film-coating systems containing polyvinyl alcohol as coating polymer, which are marketed under the tradename Opadry ® , may be used.
  • the pharmaceutical composition may further contain a HIV protease inhibitor. If present, the HIV protease inhibitor is preferably not contained in the ritonavir- containing solid dispersion.
  • the HIV protease inhibitor may be selected from darunavir, lopinavir, atazanavir, tipranavir and saquinavir.
  • the pharmaceutical composition is an optionally film-coated multi-layer tablet containing ritonavir in a first layer and the HIV protease inhibitor in a second layer.
  • the multi-layer tablet may be an optionally film-coated bilayer tablet containing ritonavir in the first layer and darunavir in the second layer.
  • the pharmaceutical composition of the present invention is suitable, optionally in combination with other antiretroviral agents, for the treatment of HIV infection, e.g. HIV-l infection.
  • the solid dispersion of the present invention may be prepared by melt-extrusion, spray-drying or spray-granulation, whereby spray-granulation is the preferred method.
  • the solid dispersion of the present invention may be prepared by i) dissolving ritonavir and the cationic polymer containing an amino group in a granulation liquid, and
  • step (i) spraying the solution obtained in step (i) onto a pharmaceutical excipient to obtain the solid dispersion in form of granules.
  • the granulation liquid is an organic solvent, preferably an alcohol, such as ethanol.
  • the pharmaceutical excipient used in method step (ii) is selected from a filler and a disintegrant.
  • the pharmaceutical composition for oral administration according to the present invention may be prepared by iii) mixing the solid dispersion of the present invention, which is preferably obtained by steps (i) and (ii) mentioned above, and a pharmaceutical excipient, and
  • step (iii) subjecting the mixture obtained in step (iii) to compression.
  • the pharmaceutical composition contains a filler and disintegrant in the solid dispersion, i.e. as intragranular compo nents, and a disintegrant, lubricant and glidant as extragranular components.
  • the HIV protease inhibitor is preferably not contained in the ritonavir- containing solid dispersion. This can be achieved by iii) mixing the solid dispersion of the present invention, which is preferably obtained by steps (i) and (ii) mentioned above, a pharmaceutical excipient and the HIV protease inhibitor, and
  • step (iii) subjecting the mixture obtained in step (iii) to compression.
  • the HIV protease inhibitor is contained in the pharmaceutical composition as extragranular component.
  • the ritonavir-containing solid dispersion is contained in a first layer and the HIV protease inhibitor is contained in a second layer of an optionally film-coated multi-layer tablet.
  • the HIV protease inhibitor is darunavir.
  • the present invention also relates to a bilayer tablet containing ritonavir in a first layer and darunavir in a second layer.
  • the optionally film-coated bilayer tablet may be prepared by i) dissolving ritonavir and the cationic polymer containing an amino group in a granulation liquid,
  • step (i) spraying the solution obtained in step (i) onto a pharmaceutical excipient to obtain a solid dispersion in the form of granules
  • step (iii) mixing the solid dispersion obtained in step (ii) and a pharmaceutical excipient, v) subjecting a mixture containing darunavir and a pharmaceutical excipient to dry-granulation,
  • step (v) mixing the granules obtained in step (v) and a pharmaceutical excipient, vii) layering the mixture obtained in step (iii) onto the mixture obtained in step (vi),
  • step (viii) subjecting the two layers obtained in step (vii) to compression, and ix) optionally subjecting the bilayer tablet obtained in step (viii) to film-coating.
  • the pharmaceutical excipient used in step (ii) is a filler and a disintegrant
  • the pharmaceutical excipient used in steps (iii) and (vi) is a disintegrant, a glidant and a lubricant
  • the pharmaceutical excipient used in step (v) is a filler and a lubricant.
  • A-l Sift all dry mix materials through appropriate sieve
  • A-2 Mix the sifted materials for appropriate time
  • A-3 Lubricate the mix with magnesium stearate
  • A-4 Compact the lubricated blend using roller compactor
  • A-6 Blend sifted granules for appropriate time
  • A-7 To the final sifted and blended granules of appropriate particle size distribution add crospovidone and colloidal silicon dioxide and mix for appropriate time
  • A-8 Lubricate the mixed product of previous step with magnesium stearate
  • step B-4 Spray granulate with the solution of step B-2 to obtain a solid solution of ritonavir within a Eudragit ® matrix

Abstract

La présente invention concerne une dispersion solide contenant du ritonavir et un polymère cationique, ainsi que l'utilisation de la dispersion solide pour la préparation d'une composition pharmaceutique pour administration orale, qui est de préférence un comprimé. La composition pharmaceutique est destinée au traitement du VIH et peut en outre contenir un inhibiteur de protéase du VIH choisi parmi le darunavir, le lopinavir, l'atazanavir, le tipranavir et le saquinavir.
PCT/EP2019/062639 2018-05-18 2019-05-16 Dispersion solide contenant du ritonavir WO2019219823A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP19725121.8A EP3793530A1 (fr) 2018-05-18 2019-05-16 Dispersion solide contenant du ritonavir

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP18173268.6 2018-05-18
EP18173268.6A EP3569225A1 (fr) 2018-05-18 2018-05-18 Dispersion solide contenant du ritonavir

Publications (1)

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WO2019219823A1 true WO2019219823A1 (fr) 2019-11-21

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EP (2) EP3569225A1 (fr)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113318076A (zh) * 2021-06-02 2021-08-31 聊城大学 一种兼具增溶及抑晶效果的利托那韦固体分散体及其制备方法
CN114557967A (zh) * 2022-03-17 2022-05-31 乐普制药科技有限公司 一种利托那韦固体分散体的制备方法
CN114668737A (zh) * 2022-03-02 2022-06-28 乐普制药科技有限公司 一种用于治疗新型冠状病毒含有利托那韦微丸的复方双层片剂

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Publication number Priority date Publication date Assignee Title
RU2759547C1 (ru) * 2020-12-04 2021-11-15 Общество с ограниченной ответственностью "АМЕДАРТ" Способ применения сополимера диметиламиноэтилметакрилата, бутилметакрилата и метилметакрилата для повышения растворимости и/или биодоступности антиретровирусной активной фармацевтической субстанции при изготовлении твёрдой дисперсии на сыпучем носителе

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000004016A2 (fr) 1998-07-20 2000-01-27 Abbott Laboratories Polymorphe de produit pharmaceutique
WO2001034118A2 (fr) 1999-11-12 2001-05-17 Abbott Laboratories Formulations pharmaceutiques de dispersion solide
DE10239999A1 (de) * 2002-08-27 2004-03-04 Röhm GmbH & Co. KG Granulat oder Pulver zur Herstellung von Überzugs- und Bindemitteln für Arzneiformen
WO2005039551A2 (fr) 2003-08-28 2005-05-06 Abbott Laboratories Forme posologique pharmaceutique solide
WO2006091529A2 (fr) 2005-02-23 2006-08-31 Abbott Laboratories Preparation pharmaceutique solide
US20070249643A1 (en) * 2003-08-28 2007-10-25 Joerg Rosenberg Solid pharmaceutical dosage form
WO2008067164A2 (fr) * 2006-11-15 2008-06-05 Abbott Laboratories Formulations de dosage pharmaceutique solides
WO2009081174A2 (fr) 2007-12-24 2009-07-02 Cipla Limited Combinaison antirétrovirale
WO2010070611A1 (fr) * 2008-12-18 2010-06-24 Ranbaxy Laboratories Limited Préparations d'atazanavir
WO2011141192A1 (fr) * 2010-05-10 2011-11-17 Evonik Röhm Gmbh Forme posologique pharmaceutique comprenant un ou plusieurs principes actifs antirétroviraux
EP2564832A1 (fr) * 2011-08-29 2013-03-06 Hexal AG Formes galéniques solides des inhibiteurs de la protéase du VIH
US20140234415A1 (en) * 2013-02-20 2014-08-21 Abbvie Inc. Tablet Dosage Forms

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000004016A2 (fr) 1998-07-20 2000-01-27 Abbott Laboratories Polymorphe de produit pharmaceutique
WO2001034118A2 (fr) 1999-11-12 2001-05-17 Abbott Laboratories Formulations pharmaceutiques de dispersion solide
DE10239999A1 (de) * 2002-08-27 2004-03-04 Röhm GmbH & Co. KG Granulat oder Pulver zur Herstellung von Überzugs- und Bindemitteln für Arzneiformen
WO2005039551A2 (fr) 2003-08-28 2005-05-06 Abbott Laboratories Forme posologique pharmaceutique solide
US20070249643A1 (en) * 2003-08-28 2007-10-25 Joerg Rosenberg Solid pharmaceutical dosage form
WO2006091529A2 (fr) 2005-02-23 2006-08-31 Abbott Laboratories Preparation pharmaceutique solide
WO2008067164A2 (fr) * 2006-11-15 2008-06-05 Abbott Laboratories Formulations de dosage pharmaceutique solides
WO2009081174A2 (fr) 2007-12-24 2009-07-02 Cipla Limited Combinaison antirétrovirale
WO2010070611A1 (fr) * 2008-12-18 2010-06-24 Ranbaxy Laboratories Limited Préparations d'atazanavir
WO2011141192A1 (fr) * 2010-05-10 2011-11-17 Evonik Röhm Gmbh Forme posologique pharmaceutique comprenant un ou plusieurs principes actifs antirétroviraux
EP2564832A1 (fr) * 2011-08-29 2013-03-06 Hexal AG Formes galéniques solides des inhibiteurs de la protéase du VIH
US20140234415A1 (en) * 2013-02-20 2014-08-21 Abbvie Inc. Tablet Dosage Forms

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF CONTROLLED RELEASE, vol. 248, 2017, pages 71 - 95

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113318076A (zh) * 2021-06-02 2021-08-31 聊城大学 一种兼具增溶及抑晶效果的利托那韦固体分散体及其制备方法
CN114668737A (zh) * 2022-03-02 2022-06-28 乐普制药科技有限公司 一种用于治疗新型冠状病毒含有利托那韦微丸的复方双层片剂
CN114557967A (zh) * 2022-03-17 2022-05-31 乐普制药科技有限公司 一种利托那韦固体分散体的制备方法
CN114557967B (zh) * 2022-03-17 2023-06-02 乐普制药科技有限公司 一种利托那韦固体分散体的制备方法

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